TY - JOUR

T1 - PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine

AU - Munir Ahmad, Shamaila

AU - Martinenaite, Evelina

AU - Hansen, Morten

AU - Junker, Niels

AU - Borch, Troels Holz

AU - Met, Özcan

AU - Donia, Marco

AU - Svane, Inge Marie

AU - Andersen, Mads Hald

PY - 2016/8/2

Y1 - 2016/8/2

N2 - We recently described naturally occurring PD-L1-specific T cells that recognize PD-L1-expressing immune cells as well as malignant cells. In the present study, we investigated whether the immunogenicity of a dendritic cell (DC)-based vaccine could be influenced by co-stimulation with a known PD-L1-derived epitope. We incubated a PD-L1-derived peptide epitope (19 amino acids long) or a control peptide (an irrelevant HIV epitope) with peripheral blood mononuclear cells from patients with malignant melanoma who had received a DC-based vaccine. We observed a significantly higher number of T cells that reacted to the vaccine in cultures that had been co-stimulated with the PD-L1 peptide epitope compared to cultures incubated with control peptide. Next, we characterized a novel PD-L1-derived epitope (23 amino acids long) and found that co-stimulation with both PD-L1 epitopes boosted the immune response elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents.

AB - We recently described naturally occurring PD-L1-specific T cells that recognize PD-L1-expressing immune cells as well as malignant cells. In the present study, we investigated whether the immunogenicity of a dendritic cell (DC)-based vaccine could be influenced by co-stimulation with a known PD-L1-derived epitope. We incubated a PD-L1-derived peptide epitope (19 amino acids long) or a control peptide (an irrelevant HIV epitope) with peripheral blood mononuclear cells from patients with malignant melanoma who had received a DC-based vaccine. We observed a significantly higher number of T cells that reacted to the vaccine in cultures that had been co-stimulated with the PD-L1 peptide epitope compared to cultures incubated with control peptide. Next, we characterized a novel PD-L1-derived epitope (23 amino acids long) and found that co-stimulation with both PD-L1 epitopes boosted the immune response elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents.

KW - Anti-tregs

KW - antigen

KW - B7-H1

KW - CD274

KW - co-stimulation

KW - dendritic cell-based vaccine

KW - melanoma

KW - PD-L1

KW - T cells

U2 - 10.1080/2162402X.2016.1202391

DO - 10.1080/2162402X.2016.1202391

M3 - Journal article

C2 - 27622072

AN - SCOPUS:84981489471

VL - 5

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 8

M1 - e1202391

ER -